We will carry out the synthesis of analogs of the thyroid hormones, thyroxine and 3,5,3'triiodothyronine, selected to answer specific questions regarding the structural, functional, and conformational requirements for hormonal activity, including antagonism to the hormones. Emphasis will be on active analogs which do not contain halogen atoms. Selected isotopically labelled analogs will be prepared for biological and physical chemical studies. Theoretical studies of selected analogs, involving molecular orbital calculations, and nuclear magnetic resonance studies of conformations of analogs and hormones in solution, will be carried out. Chemical ionization mass spectroscopic studies of the hormones and of their analogs will be used for characterization purposes. Samples will be provided for cooperative X- ray crystallographic studies. Routine rat antigoiter tests will be carried out on all compounds, and samples will be provided for cooperative biological studies of thyroxine binding globulin, tadpole metamorphosis, and metabolic effects in the rat and the sheep.